Utilizing cultures of organized CNS and PNS tissue and parallel animal models, the present proposal is designed to dissect a number of possible pathogenetic and etiologic mechanisms of relevance to the inflammatory demyelinating diseases (e.g. multiple sclerosis) and related conditions. The search for autosensitization to CNS components (myelin, oligodendrocytes) and viral antigens are major objectives. The behavior of known defective strains of SSPE virus will be observed immunocytologically in CNS tissue. Sera and lymphocytes from Strain 13 guinea pigs afflicted with chronic, progressive EAE, will be studied in CNS cultures. These samples will be taken from animals at different phases of the disease and their demyelinative capacities will be correlated with the corresponding clinical and histopathologic pictures. Using IgG conjugated to HRP, the site of action of humoral demyelinating factors will be sought. In addition, guinea pigs sensitized against purified oligodendrocytes will be studied and their sera tested upon CNS cultures and studied by EM and immunocytochemistry. Using immunocytochemical technology, viral antigens will be sought in frozen sections of acute and chronic MS plaques and with the aid of IgG from the serum and CSF of MS subjects (versus non-MS subjects), attempts will be made to determine whether or not MS serum or CSF contains any specific binding capacity for CNS tissue.